A large number of diverse products, including drugs, aerosols, household products, and cosmetics, are presently tested for biocompatibility. Biocompatibility, which embraces positive or compatible reactions and negative or toxcological effects, is a term used to describe a wide range of reactions with biological, particularly mammalian, tissue. In fact, many products which can come in contact with eyes, skin, mucous membranes, or other organs are routinely tested for biocompatibility. Contact with these materials may be initiated by a variety of means, such as topical application, inhalation, or ingestion.
The United States Food and Drug Administration, as well as other governmental agencies, request that manufacturers supply information on biocompatibility, particularly toxicological effects, on most products which may come accidently or intentionally into contact with eye, skin or mucous membranes. The protocols for many biocompatibility tests require the use of live animals. Many conventional tests for biocompatibility cause rashes or other irritations of the skin, mucous membranes and ocular tissue on the test animal. Public concern over the use of live animals in research, as well as in biocompatibility testing, is one problem which has led to a search for alternative test methods. Other problems are that these standard procedures for testing are subjective, not easily quantified and do not always mimic the effects on humans; rather, the procedures are used because they show an easily identifiable, high level response.
The Draize test, which is used to determine the toxicological effect of a variety of substances including cosmetics and household products on eyes, is one test which has been criticized. In the standard Draize test, the substance to be tested is placed into the lower conjunctival sac of rabbit eyes and the eyes are monitored for extent and duration of injury. The Food and Drug Administration has suggested a modified Draize test as the preferred method of eye irritancy evaluation (Federal Hazards Substances Act (1964)). This modification uses six rabbits, rather than the nine rabbits of the original Draize test, but is otherwise substantially the same. While other tests have been proposed to replace the Draize test, none are widely used.
The Draize test, both in its original and modified forms, has been criticized on the basis of humane considerations, discrepancies in response between rabbit and human eyes, the subjective nature of the scoring system, and difficulties in interpreting test results because of interlaboratory variability on tests with identical materials. A review article by the Office of Pesticides and Toxic Substances of the United States Environmental Protection Agency and entitled "Eye Irritation Testing", EPA-560/11-82-001, discusses the Draize test, its modifications, and a number of the criticisms which have been made of the current methods of eye irritancy testing.
Accordingly, an object of the invention is to provide an in vitro method of testing the biocompatibility of a variety of substances and for use in lieu of in vivo testing.
Another object is to provide a method of testing ocular irritancy of a variety of substances without the use of laboratory animals.
A further object is to provide a test for ocular irritancy of substances which has a high correlation to effects on humans.
A still further object is to provide an improved in vitro method of toxicological testing.
These and other objects and features of the invention will be apparent from the following description and the drawing.